Background & Aims: Following the changes in substance abuse pattern and its consequences in Iran, especially constant cognitive impairments resulting from their use, this study aimed to compare working memory in psychotic patients who use methamphetamine and patients with hepatitis C and methamphetamine users with hepatitis C virus.

Materials & Methods: In this casual-comparative study, a total of 90 patients of Razi hospital in Tehran and AIDS Research Center at Tehran University who met the inclusion criteria were selected through convenient sampling. The n-back test (Kirchner, 1958) was used in the current study. Data were analyzed by the central and dispersion indexes and the Multivariate Analysis of Variance as well as the Tukey test.

Results: There was a significant difference between the three groups in working memory components (overall score = p < 0.01, incorrect answer and reaction time = p < 0.001). According to the results of the post hoc test, the average of the overall score for psychotic patients who use methamphetamine was significantly less and the average of the incorrect answer was more than the other two groups, also the average reaction time was lower than the other two groups.

Conclusion: Long-term use of methamphetamine causes impairment in working memory through creating neuropsychological damage in brain regions, which in turn leads to deficits in executive functions, attention and so on. Therefore, in addition to help in better understanding of the problem, reducing relapses, frequent hospitalizations and other negative outcomes, identifying these factors could lead to different therapeutic strategies.